Management of Transplant Renal Artery Pseudoaneurysm and Literature Review

Renal transplantation is the ultimate treatment for end-stage renal disease patients. However, vascular complications can impact renal allograft outcomes. Extrarenal pseudoaneurysms (EPSA) are a rare complication occurring in 1% of transplant recipients. We report a case series of extrarenal pseudoaneurysm after kidney transplant with different clinical presentations and management strategies. Given the rarity of EPSA, literature describing this complication is limited to single case reports or small retrospective case series. We also provide an up-to-date review of 76 articles on mycotic, bacterial, and idiopathic EPSAs. Allograft removal is considered standard treatment, but new endovascular alternatives may allow allograft salvage. EPSA should be managed with a multidisciplinary approach. Surveillance with renal ultrasound is recommended in patients considered high risk.


Introduction
Vascular complications, which have an incidence rate of 6-30% after a kidney transplant, can impact allograft and patient outcomes [1]. Vascular complications include renal artery stenosis, arterial/venous thrombosis, arteriovenous fistulas, and renal artery pseudoaneurysms [1]. Intrarenal pseudoaneurysms are most commonly secondary to percutaneous kidney biopsy, infection, or technical error but usually resolve spontaneously with time, despite a 5% occurrence rate [2]. Extrarenal pseudoaneurysms (EPSAs) carry an incidence rate of 1% and cause irreversible arterial destruction of the vessel wall; causes can include infectious and noninfectious etiologies [1,3,4]. Despite their rarity, EPSAs are a serious complication, which profoundly impact both graft and patient survival. Though small EPSAs can be closely observed, large or infected EPSAs are a clinical emergency. Rupture of the EPSA creates life-threatening bleeding, so allograft nephrectomy, either prophylactically or emergently, is the recommended treatment of choice [5][6][7].
Evidence-based care of this complication is limited to single case reports or small retrospective series. Here, we report three cases of infectious EPSA after kidney transplantation, including their wide-ranging clinical presentations, treatments, and outcomes (Table 1). Additionally, we present an up-to-date review of the literature to provide the reader with a multitude of examples of how this anomaly may present in practice (Table 2).

Case Presentation
2.1. Case 1 (Figure 1). The patient was a 68-year-old male with end stage renal disease (ESRD) secondary to Wegener's granulomatosis who received his second deceased donor kidney transplant (DDKT) in November 2019. His postoperative course was significant for delayed graft function secondary to acute tubular necrosis (ATN). On postoperative day (POD) 19, he presented to clinic with complaints of fatigue, chills, and rigors. He was diagnosed with urosepsis. Both blood and urine cultures on admission grew   Pseudomonas aeruginosa. Patient was started on broad spectrum antibiotics which included clindamycin, piperacillin/tazobactam, then cefepime and tobramycin at various points. A noncontrast computer tomography (CT) scan of the abdomen pelvis on admission was negative for any perinephric fluid collection. Overnight, he acutely decompensated and coded. Advanced cardiac life support protocol was initiated with return of spontaneous circulation after 20 minutes. Repeat CT angiogram (CTA) of the abdomen/ pelvis was notable for a large retroperitoneal hematoma with active bleed from EPSA of the donor renal artery. Interventional radiology (IR) was consulted for placement of a covered stent. This intervention was unsuccessful, and ultimately, the patient was taken to the operating room and underwent transplant nephrectomy and saphenous vein patch angioplasty of the external iliac artery. The donor renal artery was completely avulsed from the recipient artery at the anastomosis site.
The patient remained in the intensive care unit (ICU) postoperatively secondary to septic shock and multiorgan failure. On POD 39, he died of septic shock secondary to ischemic bowel and bowel perforation. Interestingly, the liver recipient from the same cadaveric donor, who was transplanted at another institution, also died suddenly at home.   Figure 2). The patient is a 63-year-old male with ESRD secondary to diabetes and hypertension who received a DDKT in January 2020. The patient's immediate postop course was complicated by wound infection and dehiscence requiring multiple wash outs and biological mesh repair. Almost six months posttransplant, he was presented to a routine clinic follow-up with 1 week history of right flank pain, elevated blood pressure, hematuria, and a leaking sinus at his Gibson incision. Labs were significant for anemia and acute kidney injury with serum creatinine of 7 mg/dL from a baseline of 2 mg/dL.
Ultrasound showed a juxta-anastomotic pseudoaneurysm measuring 5 × 5 cm confirmed on CT with concern for a contained anastomotic leak. The patient was admitted to ICU and started on broad spectrum antimicrobials empirically, which included metronidazole, vancomycin, and micafungin. Blood and urine cultures from admission grew Enterococcus faecalis. Vascular surgery performed an angiogram that showed an anastomotic pseudoaneurysm, but it was deemed unsafe to coil due to a wide neck.
After detailed discussion with the patient, we decided to proceed with a Gore excluder cover stent placement in the external iliac artery with loss of the transplanted kidney because of the expanding pseudoaneurysm. Surgical repair option was discussed but considered too high risk for this patient and still carried a significant chance of graft loss.

Case Reports in Transplantation
After stent deployment, CTA confirmed an excluded pseudoaneurysm with no evidence of leak. Transthoracic and transesophageal echocardiograms showed no vegetation or evidence of endocarditis. Repeat blood and urine cultures on hospital days 3 and 5 were negative, and his antibiotic regimen was changed to ampicillin monotherapy. The patient was restarted on hemodialysis and discharged to an inpatient rehab facility to finish a six-week antibiotic course. The patient is still alive and awaits a second kidney transplant. Figure 3).  7 Case Reports in Transplantation respectively. There was no anastomotic EPSA. The distal transplant renal artery was severely stenosed but patent. Due to nonavailability of customized cover stent, the procedure was performed in two stages. Initially, the IR team coil embolized the larger EPSA, and she returned to IR the following day for placement of two 6 mm × 20 mm covered stents with angioplasty of the distal transplant renal artery. Repeat inpatient blood cultures were negative. She was discharged home on a four-week course of linezolid and fluconazole to cover the VRE and previous Candida tropicalis. The patient is doing well, and her repeat urine and blood cultures have remained negative of antimicrobials.

Discussion
EPSA is a rare (1% incidence rate) but devastating complication of kidney transplantation. EPSA can occur at or adjacent to the surgical anastomosis, usually secondary to a mycotic or bacterial infection. Previous literature reviews place the incidence of allograft loss at 56%, concurrence with an infective pathogen at 62%, and mortality at 14% [8]. In multiple retrospective series, C. albicans was the leading pathogen in cases with infection [8][9][10]. The mechanism by which mycotic and bacterial pseudoaneurysms develop is well-described in the literature, involving an inflammatory process that invades and compromises the wall of the artery [11].
Patients with kidney transplants often have multiple risk factors for opportunistic infections, including immunosuppression, end-stage renal failure, diabetes mellitus, hypertension, and dyslipidemia [12][13][14]. Additionally, prolonged ICU stays (>7 days) and extended operative times are associated with increased incidence [15]. Intuitively, age should be a risk factor for all operative complications, but this association is not reflected in the data [16]. Procurement of organs, transportation, back-table preparation, and transplantation involve countless opportunities for inadvertent contamination; the likelihood of transplant contamination is estimated at 40% [12]. This prevalence highlights the importance of obtaining donor cultures from multiple sites, careful handling of the allograft, and strict sterile technique at all times. Organ procurement organizations (OPO) work extensively with the donor centers to ensure minimal infection risk, frequently involving infectious disease colleagues to confirm thorough treatment and prophylaxis. While we extensively scan donors, preservation fluid, and recipient blood cultures, some smoldering infections can be masked or subdued by extended courses of antibiotics, making detection of some pathogens difficult [14].
The clinical presentation of EPSAs varies considerably, evident both within our own cases and the literature. Patients can be totally asymptomatic (Case 3) or acutely decompensating from aneurysmal rupture (Case 1). Time to diagnosis varied both within our own case series as well as cases in literature, ranging from a few days to many years after the initial transplant. Other symptoms include pulsatile masses, abdominal tenderness, lower limb ischemia, allograft dysfunction, anemia, or signs of infection [4,15,17]. Doppler ultrasonography is the first imaging tool used, ideally showing the pathognomonic "Yin Yang" sign indicating turbulent mixing of blood as exhibited in Figures 2(b) and 3(b). CT or magnetic resonance (MR) angiography can confirm the pathology as well as evaluate its impact on surrounding structures such as the ureter or iliac vessels [18]. Conventional angiography elucidates the exact location and occasionally allows for simultaneous percutaneous treatment.
All three of our cases presented with an associated infection. In Case 1, Pseudomonas aeruginosa grew in urine and blood cultures; per literature review, this is the most frequent bacteria associated with EPSA occurrence [8,11]. Rapidly developing an EPSA in less than 3 weeks, Case 1 is a good reminder that all infections, especially pathogens historically linked to the formation of EPSAs such as Pseudomonas, should trigger aggressive, immediate treatment, and surveillance after antibiotic completion. Case 2 is notable as Enterococcus faecalis has only been associated with EPSA in one other case in the literature. Notably, Case 3 had multiple UTIs prior to discovering the EPSA, but no positive blood cultures. In this instance, it is possible that long-term treatment for her multiple UTIs masked a developing vascular insult, at which point the EPSA was incidentally noted.
Indications for repair of an EPSA are controversial, but pseudoaneurysms with a diameter of >2.5 cm are almost uniformly at a high risk of rupture [1,7,15,16,19]. Additional intervention indications include symptom severity, rate of size enlargement, presence of infection, and renal artery hypertension [1,15]. EPSAs smaller than 2 cm can usually be managed conservatively with serial imaging and resolve spontaneously in some cases [20]. Therapeutic options for large or high-risk EPSAs include allograft nephrectomy, conventional open repair (allograft removal, creation of new vascular anastomoses, and repair of previous site with patch angioplasty), endovascular stenting or coiling, and/or ultrasound-guided percutaneous thrombin injection [14,21]. In both our own practice and literature review, transplant nephrectomy represented the gold standard for definitive treatment but is a tough decision. Endovascular intervention represents a promising future for repair that retains allograft function, but, as in Case 2, sometimes necessitates excluding the allograft to prevent rupture. In such scenarios, a transplant nephrectomy may be performed later based on the patient's clinical condition (development of allograft abscess, etc.). The authors, including Lin et al. and Cano-Velasco et al., have compiled past articles on this subject, and Cano-Velasco et al. proposed a treatment algorithm based on these reports [8,16].
Management of EPSA requires a multidisciplinary approach. Patient and allograft salvage are the prime goal.
Newer endovascular techniques open new options for salvaging the graft. Each case is different and needs thorough assessment and unique plan development based on the patient's needs.

Conclusion
EPSA of the transplant renal artery is a rare issue. Prevention, high degree of suspicion, and aggressive multidisciplinary management are needed to save the patient and renal 8 Case Reports in Transplantation allograft. Surveillance of patients with previous urinary or bloodstream infections is also recommended.

Data Availability
The articles referenced in this publication are available online through a multitude of article databases and publisher websites.

Consent
We obtained written consent for publication from our two living patients and obtained verbal consent for publication from our deceased patient's next-of-kin.